Publications of Philippe ERNEST
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See detailLa complémentarité entre essais cliniques contrôlés et registres observationnels : L'exemple des études de prévention cardiovasculaire avec les inhibiteurs des SGLT2
Scheen, André ULiege; ERNEST, Philippe ULiege; JANDRAIN, Bernard ULiege

in Revue Médicale de Liège (2017), 72(12), 563-568

Evidence-based medicine (EBM) is mainly supported by the results of randomised controlled trials (RCTs). If the latter offer guarantees of reliability, especially by minimizing the influence of ... [more ▼]

Evidence-based medicine (EBM) is mainly supported by the results of randomised controlled trials (RCTs). If the latter offer guarantees of reliability, especially by minimizing the influence of confounding factors and potential biases, they also have limitations. Observational databases resulting from real life registries, if possible build in a prospective manner, may offer some solutions, but are also exposed to limitations. This article compares the advantages and disadvantages of the two sources of information, which ideally should be complementary. For the purpose of illustration, we shall compare the recent results of RCTs and of observational databases from multinational registries that investigated the effects of sodium-glucose cotransporter type 2 inhibitors (gliflozins) on cardiovascular outcomes in patients with type 2 diabetes. [less ▲]

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See detailProtection cardio-renale par les inhibiteurs des SGLT2 (gliflozines) : d'EMPA-REG OUTCOME a CANVAS.
Scheen, André ULiege; Ernest, Philippe ULiege; Jandrain, Bernard ULiege

in Revue Médicale Suisse (2017), 13(571), 1421-1426

The cardiovascular (CV) and renal protection reported with empagliflozin in EMPA-REG OUTCOME is now confirmed with canagliflozin in CANVAS in patients with type 2 diabetes and high cardiovascular risk ... [more ▼]

The cardiovascular (CV) and renal protection reported with empagliflozin in EMPA-REG OUTCOME is now confirmed with canagliflozin in CANVAS in patients with type 2 diabetes and high cardiovascular risk: similar and significant reductions in major CV events (-14 vs. -14%), in hospitalisations for heart failure (-35 vs. -33%) and in renal events (-39 vs. -40%). The greater reduction in CV mortality (-38 vs. - 13%) and all-cause mortality (-32 vs. -13%) in EMPA-REG OUTCOME than in CANVAS may be explained by the greater proportion of patients with CV disease (secondary prevention : 99 vs. 65%). In contrast to EMPA-REG OUTCOME, CANVAS did not show an increase in stroke (-10%, NS), but reported a higher rate of fractures and amputations with canagliflozin. Overall, these results support a class effect for the cardiorenal protection by inhibitors of sodium-glucose type 2 (SGLT2) cotransporters. [less ▲]

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See detailProtection cardiovasculaire du patient diabetique de type 2 : d'EMPA-REG OUTCOME a LEADER.
Scheen, André ULiege; WALLEMACQ, Caroline ULiege; Jandrain, Bernard ULiege et al

in Revue Médicale Suisse (2016), 12(527), 1370-1375

Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with type 2 diabetes and high cardiovascular risk. Empagliflozin, an inhibitor of sodium-glucose type ... [more ▼]

Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with type 2 diabetes and high cardiovascular risk. Empagliflozin, an inhibitor of sodium-glucose type 2 (SGLT2) cotransporters, in EMPA-REG OUTCOME, and liraglutide, an agonist of glucagon-like peptide-1 (GLP-1) receptors, in LEADER, showed a significant reduction in major cardiovascular events (- 14 and - 13 %, respectively), cardiovascular mortality (- 38 and - 22 %, respectively) and all-cause mortality (- 32 and - 15 %, respectively). A lower progression of kidney disease and less renal events were also reported. The underlying protective mechanisms remain controverted as the discussion whether the benefits are specific to each medication or could be extended to other molecules of these two pharmacological classes. [less ▲]

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See detailForces et faiblesse des essais cliniques . Evolution en fonction de l'essor de la medecine personnalisee.
Ernest, Philippe ULiege; Jandrain, Bernard ULiege; Scheen, Andre ULiege

in Revue Médicale de Liège (2015), 70(5-6), 232-6

Randomised Controlled Trials (RCTs) represent the cornerstone of Evidence-Based Medicine (EBM). Based upon the rules of Good Clinical Practice (GCP), they offer many strengths but also present some ... [more ▼]

Randomised Controlled Trials (RCTs) represent the cornerstone of Evidence-Based Medicine (EBM). Based upon the rules of Good Clinical Practice (GCP), they offer many strengths but also present some weaknesses. The rigorous methodology used allows avoid bias related to confounding factors (through a control group), selection bias (through randomisation) and interpretation bias (through double blinding). However, patients recruited in clinical trials and study experimental conditions markedly differ from the situation in real life. Furthermore, clinical trials recruit a mix of good and poor responders, so that the average therapeutic response is most often mitigated. Clinical trials must evolve according to the new concepts of personalized medicine to become even more performing. In a near future, they must progress from a statistical analysis on large cohorts of patients to a more individualized analysis guided by patient phenotype and genotype characteristics. [less ▲]

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See detailComment j’explore …Une différence de risque de survenue d’un événement dans les études cliniques
SCHEEN, André ULiege; ERNEST, Philippe ULiege; JANDRAIN, Bernard ULiege

in Revue Médicale de Liège (2012), 67(11), 597-602

Evidence-based medicine often requires the comparison of two therapeutic interventions in controlled clinical trials with the demonstration of a superiority (versus a placebo or an active comparator) or ... [more ▼]

Evidence-based medicine often requires the comparison of two therapeutic interventions in controlled clinical trials with the demonstration of a superiority (versus a placebo or an active comparator) or at least a non-inferiority (versus an active reference) concerning a primary endpoint that has been defined a priori (occurrence of a major clinical event, for instance). The difference in the occurrence of such an event between two treatments may be statistically analyzed by absolute risk reduction, relative risk reduction, hazard ratio or odds ratio. The present article discusses the nuances, sometimes of importance, concerning the significance of these various indices and analyses the cautions to be taken and the pitfalls to be avoided in their interpretation and use in practice. The clinician is, indeed, increasingly confronted to results of clinical trials, but is generally poorly informed regarding the nuances of these various statistical analyses. [less ▲]

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See detailInhibiteurs du cotransporteur du glucose SGLT rénal pour traiter le diabète de type 2
SCHEEN, André ULiege; RADERMECKER, Régis ULiege; ERNEST, Philippe ULiege et al

in Revue Médicale Suisse (2011), 7(306), 1621-1629

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See detailInhibiteurs du cotransporteur du glucose SGLT2 renal pour traiter le diabete de type 2.
SCHEEN, André ULiege; Radermecker, Régis ULiege; Ernest, Philippe ULiege et al

in Revue Médicale Suisse (2011), 7(306), 1621-41626-9

Kidney plays a role in glucose homeostasis, not only by its capacity to produce glucose through local gluconeogenesis, but also, and even more important in presence of diabetes, by its capacity to excrete ... [more ▼]

Kidney plays a role in glucose homeostasis, not only by its capacity to produce glucose through local gluconeogenesis, but also, and even more important in presence of diabetes, by its capacity to excrete glucose in urine when hyperglycaemia exceeds tubular reabsorption threshold. Such reabsorption depends on sodium-glucose cotransporters-2 (SGLT2), which can be blocked by selective inhibitors. These pharmacological agents augment glucosuria and reduce hyperglycaemia independently of insulin. Some have already proven their efficacy to improve glucose control, in monotherapy or in combination, while promoting weight loss and without inducing hypoglycaemia. Dapagliflozin should be the first medication of this new pharmacological class to be commercialized for the management of type 2 diabetes. [less ▲]

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See detailStrategies pour eviter l'inertie et la non-observance dans les essais cliniques.
Jandrain, Bernard ULiege; Ernest, Philippe ULiege; Radermecker, Régis ULiege et al

in Revue Médicale de Liège (2010), 65(5-6), 246-9

Randomised controlled trials play a key role in evidence-based medicine as far as the assessment of both efficacy and safety of drugs is concerned. Various strategies are used to avoid physician's inertia ... [more ▼]

Randomised controlled trials play a key role in evidence-based medicine as far as the assessment of both efficacy and safety of drugs is concerned. Various strategies are used to avoid physician's inertia and to combat patient's non compliance, two pitfalls that may hinder the demonstration of the therapeutic efficacy of the drug. Clinical inertia may be limited by titration, forced or optional, driven by therapeutic targets, or by the use, if necessary, of rescue medications. Compliance may be verified by "pill count". This simple technique allows to exclude non compliant patients when they are detected during the placebo run-in period before randomisation or not to take into account patients with poor compliance in the final evaluation by using a statistical analysis restricted to individuals who have strictly adhered to the study protocol ("per protocol analysis"). Self-monitoring and patient's empowerment in the treatment also contribute to improve drug compliance. Clinicians may take advantage of these approaches derived from clinical trials to improve their daily practice. [less ▲]

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See detailLe traitement du diabète de type 2: entre insulinosensibilisateurs et insulinosécrétagogues
SCHEEN, André ULiege; RADERMECKER, Régis ULiege; Philips, J. C. et al

in Revue Médicale de Liège (2007), 62 Spec No

Type 2 diabetes is a complex disease characterized by a dual defect of insulin secretion and insulin sensitivity, which may vary from patient to patient, but also along the natural history of the disease ... [more ▼]

Type 2 diabetes is a complex disease characterized by a dual defect of insulin secretion and insulin sensitivity, which may vary from patient to patient, but also along the natural history of the disease in a particular patient. Besides the lifestyle changes, the treatment strategy comprises the administration of agents that promote insulin secretion and/or that improve insulin sensitivity. Drugs facilitating weight loss also improve glucose control by reducing insulin resistance. A global approach should be recommended to reduce the high cardiovascular risk of diabetic patients. The present article aims at summarizing our contribution to the development of drugs designed for the treatment of type 2 diabetes. [less ▲]

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See detailPrevention du diabete de type 2: style de vie ou medicaments?
Scheen, André ULiege; Letiexhe, Michel ULiege; Ernest, Philippe ULiege

in Revue Médicale de Liège (2003), 58(4), 206-10

The World Health Organisation strongly recommends strategies for the prevention of type 2 diabetes, knowing the epidemics of the disease and its strong association with that of obesity. Several ... [more ▼]

The World Health Organisation strongly recommends strategies for the prevention of type 2 diabetes, knowing the epidemics of the disease and its strong association with that of obesity. Several intervention studies, in China ("Da-Qing Study"), in Europe ("Malmo study", "Finnish Diabetes Prevention Study") and in the United States ("Diabetes Prevention Program"), showed that lifestyle change are able to reduce by around 50% the incidence of type 2 diabetes in at risk individuals. Various pharmacological approaches have also proven their efficacy in preventing type 2 diabetes, but in most cases with less impressive reductions, between 25% and 35%. It is the case for metformin, acarbose, orlistat or various inhibitors of the renin-angiotensin system. After the report of promising results with troglitazone, large prospective studies are ongoing to test the efficacy of rosiglitazone and pioglitazone in such an indication, two insulinsensitizers of the thiazolidinedione family. We will briefly described the main results of intervention studies to prevent type 2 diabetes in at risk subjects, because of the presence of obesity, impaired glucose tolerance and/or arterial hypertension. [less ▲]

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See detailNew antiobesity agents in type 2 diabetes: overview of clinical trials with sibutramine and orlistat.
Scheen, André ULiege; Ernest, Philippe ULiege

in Diabetes and Metabolism (2002), 28(6 Pt 1), 437-45

Besides genetic predisposition, obesity is the most important risk factor for the development of type 2 diabetes mellitus. Even modest weight reduction can improve blood glucose control in overweight ... [more ▼]

Besides genetic predisposition, obesity is the most important risk factor for the development of type 2 diabetes mellitus. Even modest weight reduction can improve blood glucose control in overweight subjects. After failure of lifestyle modifications, antiobesity drugs such as orlistat, a potent and selective inhibitor of gastric and pancreatic lipases that reduces lipid intestinal absorption, or sibutramine, a noradrenaline and 5-hydroxytryptamine reuptake inhibitor that regulates food intake, may be considered to favour weight loss and/or weight maintenance. Several placebo-controlled studies have recently demonstrated that both drugs are able to promote weight loss in obese type 2 diabetic patients treated with diet alone, sulphonylureas, metformin or insulin. The greater weight reduction as compared to placebo was associated with a significant reduction of glycated haemoglobin levels and/or of the doses of classical antihyperglycaemic agents, especially in good responders who lost at least 10% of initial body weight. In addition, vascular risk factors associated to insulin resistance were also reduced after weight loss. These antiobesity agents may also contribute to delay or prevent the progression from impaired glucose tolerance to overt type 2 diabetes in at risk obese individuals ("Xenical in the prevention of diabetes in obese subjects" trial). Large long-term prospective studies, such as the "Sibutramine cardiovascular and diabetes outcome study" should better determine the place of pharmacological anti-obesity strategy in the overall management of obese patients with impaired glucose tolerance or type 2 diabetes. [less ▲]

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